LUNG CANCER

 

WHERE TO FIND US

• MFT - Wythenshawe Hospital
• The Christie NHS Foundation Trust
• MCRC building
• CRUK MI
• The University of Manchester

Manchester has played a key role in the evolution of lung cancer treatment: its doctors have led international trials of novel chemotherapeutic agents, targeted therapies and, most recently, immunotherapy combinations. Within the UK, Greater Manchester recruits more lung cancer patients than anywhere else into clinical trials.

Our lung cancer group is strong, with diverse research interests from discovery science through to clinical application. These strengths are recognised within the themes of the Cancer Research UK Lung Cancer Centre of Excellence at Manchester and UCL, which was established in 2014.

Within discovery science, researchers are harnessing genomic data and bioinformatics approaches to explore the role of novel cell kinases in radiosensitivity. Other groups are investigating the role of mutant p53 in chemoresistance and metastasis and of the RAC pathway in controlling migration and invasion and in lung tumourigenesis.

Prevention and early detection are important areas for us – our lung cancer screening project combines risk stratification and engaging with hard to reach communities, and the pilot has demonstrated an ability to shift diagnosis from late to early stage disease. We are also interested in survivorship, and we are looking at ways to track tumour evolution and detect minimal residual disease.

Translational research is focused on liquid biopsy and minimally invasive methods to stratify, predict sensitivity, catch relapse and identify resistance mechanisms. Circulating tumour cell (CTC) derived explant models (CDX) recapitulate the biology of individual patients and mirror response to treatment, offering a more relevant pre-clinical platform for investigating the disease.

In radiotherapy, we lead national and international trials evaluating novel radiotherapy technologies and combination of systemic treatment and radiotherapy. The arrival of proton therapy and MR-guided radiotherapy offers exciting new opportunities in this field. By harnessing big data and theragnostics – combining imaging and patient reported outcomes – we aim to further individualise treatment and improve outcome. Biomarkers are at the heart of our clinical trials: gene signatures and imaging-based measures of hypoxia both offer the chance to intensify or adapt radiotherapy where necessary.

CURRENT RESEARCH QUESTIONS

Target and therapeutics development (Lead: Fiona Blackhall):

  • What are the molecular and clinical characteristics in an individual that can be used to select the therapy or therapy combination with the highest chance of benefit and lowest chance of toxicity?
  • How can chemotherapy, targeted therapies and immunotherapies be combined and/or sequenced to obtain the best clinical outcome for an individual patient with lung cancer?

Early Phase Drug Development (Lead: Matthew Krebs)

  • Can clinical outcomes be improved by matching patients to relevant early phase trials of novel therapeutic agents based on molecular characteristics of tumour or ctDNA (TARGET programme)?

Early Detection (Lead: Philip Crosbie)

  • Can implementing a lung cancer screening programme model targeting the traditionally ‘hard to reach’ populations improve lung cancer survivorship by detecting lung cancer earlier?
  • Can the implementation of cutting edge biomarkers as part of lung cancer screening programmes lead to better and faster diagnostics?

Biomarker research (Lead: Caroline Dive)

  • Can blood tests (liquid biopsies) be used to detect relapse early and identify drug resistance mechanisms?
  • Can blood tests (liquid biopsies) be used to stratify for sequential personalised therapies?​

Radiotherapy/big data/Theragnostics (Lead: Corinne Faivre-Finn)

  • Can we provide evidence and individualise treatment in patients who are typically excluded from clinical trials?
  • Can we personalise radiotherapy treatment based on circulating biomarkers and functional imaging?
  • Can we demonstrate the benefit of advanced radiotherapy techniques such as MR-linac and protons?​

Patient Centred Research (Lead: Janelle Yorke)

  • Can a number of strategies be implemented to place patients at the centre of research design and practice in order to improve outcomes and quality of life for people living with lung cancer?

KEY PUBLICATIONS

First-line crizotinib versus chemotherapy in ALK-positive lung cancer.
Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F.
N Engl J Med. 2014 Dec 4;371(23):2167-77. 

Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer.
Carter L, Rothwell DG, Mesquita B, Smowton C, Leong HS, Fernandez-Gutierrez F, Li Y, Burt DJ, Antonello J, Morrow CJ, Hodgkinson CL, Morris K, Priest L, Carter M, Miller C, Hughes A, Blackhall F, Dive C, Brady G.
Nat Med. 2017 Jan;23(1):114-119. doi: 10.1038/nm.4239. 

Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial.
Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, Bezjak A, Cardenal F, Fournel P, Harden S, Le Pechoux C, McMenemin R, Mohammed N, O'Brien M, Pantarotto J, Surmont V, Van Meerbeeck JP, Woll PJ, Lorigan P, Blackhall F; CONVERT Study Team.
Lancet Oncol. 2017 Jun 19. pii: S1470-2045(17)30318-2. doi: 10.1016/S1470-2045(17)30318-2. 

Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer.
Ciuleanu TE, Ahmed S, Kim JH, Mezger J, Park K, Thomas M, Chen J, Poondru S, VanTornout JM, Whitcomb D, Blackhall F.
Br J Cancer. 2017 Aug 3. doi: 10.1038/bjc.2017.226.

Assessment of Breathlessness in Lung Cancer: Psychometric Properties of the Dyspnea-12 Questionnaire.
Tan JY, Yorke J, Harle A, Smith J, Blackhall F, Pilling M, Molassiotis A.
J Pain Symptom Manage. 2017 Feb;53(2):208-215. 

Implementing lung cancer screening: baseline results from a community-based 'Lung Health Check' pilot in deprived areas of Manchester.
Crosbie PA, Balata H, Evison M, Atack M, Bayliss-Brideaux V, Colligan D, Duerden R, Eaglesfield J, Edwards T, Elton P, Foster J, Greaves M, Hayler G, Higgins C, Howells J, Irion K, Karunaratne D, Kelly J, King Z, Manson S, Mellor S, Miller D, Myerscough A, Newton T, O'Leary M, Pearson R, Pickford J, Sawyer R, Screaton NJ, Sharman A, Simmons M, Smith E, Taylor B, Taylor S, Walsham A, Watts A, Whittaker J, Yarnell L, Threlfall A, Barber PV, Tonge J, Booton R.
Thorax. 2018 Feb 13. pii: thoraxjnl-2017-211377. 

WHO'S WHO

Nursing

  • Glenda Laviste
  • Nicky Moore
  • Marie Kirwan
  • Fiona McCartin
  • Sharon Woolley
  • Janelle Yorke

Clinical Fellows

  • Tiana Kordbacheh
  • Rebecca Tay
  • Fabio Gomes
  • Maryam Ahmed
  • Haval Balata
  • Tim Edwards
  • Anna Moss

Clinical Genetics

Histopathology

Surgery

Biology

Bioinformatics

Physics

Genomics

  • Andrew Wallace
  • Nick Hickson
  • George Burhgel
  • Jade Harris